Effect of JNK3-N-Tat on MPP⁺/MPTP-induced neuronal death in PD models.

<p>(A) Pretreatment with 20 μM JNK3-N-Tat resulted in a significant attenuation of MPP⁺-induced SH-SY5Y cell death. *<i>P</i><0.05 versus vehicle-MPP⁺; #<i>P</i>>0.05 versus vehicle-MPP⁺. (B, C) Animals were sacrificed 7 days post-MPTP administration to characterize the loss of dopaminergic neurons. Representative images from immunostained sections of the SNc and the striatum from the sham-treated normal control group (i), the group of mice administered saline prior to MPP⁺ treatment (ii), and the groups of mice administered JNK3-N-Tat (iii) or JNK3-4A-Tat (iv) preceding MPTP injection. The results revealed that treatment with JNK3-N-Tat caused a significant decrease in neurodegeneration in the SNc and also attenuated MPTP-induced striatal DA terminal loss, whereas treatment with JNK3-4A-Tat had no effect. Scale bars in B(i–iv): 1 = 10μm; Scale bars in C(i–iv): 1 = 100 μm. (D, E) Quantitative analysis of the protective effects of JNK3-N-Tat on MPTP-induced mesencephalic dopaminergic neuronal damage. The numbers of surviving TH-positive cells in the SNc and TH-positive fibers in the striatum were counted. The data are expressed as the mean±SD values (n = 6 animals per group). (F) In primary cultured cortical neurons, our results revealed that pretreatment with 20 μM JNK3-N-Tat 1 hr before MPP⁺(100 μM) treatment resulted in significant attenuation of cell death. (G, H) Immunofluorescence stainings using an anti-MAP2 antibody revealed that JNK3-N-Tat treatment decreased the loss of MAP2-positive neurons (20× magnification). a: <i>P</i><0.05 versus Normal control; b: <i>P</i><0.05 versus vehicle; c: <i>P</i><0.05 versus JNK3-N-Tat; d: <i>P</i>>0.05 versus vehicle.